Program Director/Principal Investigator (Last, First Middle): Bell, Thomas J. Project Summary: The development of effective treatments or cures for a wide range of diseases requires translational studies that are directly relevant to human pathophysiology. The use of human biospecimens plays a key role in accelerating scientific discoveries in neurological research by providing scientists with a direct experimental model system to advance understanding of pathogenesis and treatment of neurological disease, including Alzheimer's disease and related dementias (AD/ADRD). To address several complex issues facing AD/ADRD research, including disease etiology as well as the development of improved diagnostics and treatment strategies, investigators require access to a unique human tissue resource that could provide rigorous and uniform collection of human biospecimens from defined cohorts of both post mortem AD/ADRD donors and living AD/ADRD patients to yield consistent and reproducible experimental results for inventive and groundbreaking studies. As a leading human tissue provider for the biomedical research community, the National Disease Research Interchange (NDRI) is a 501(c)(3), not-for-profit organization that remains at the forefront of coordinating biospecimen procurement to match the needs of advancing scientific experimental methodologies, enabling cutting-edge research. For over 30 years, NDRI has received NIH funding for the parent award to this administrative supplement, the Human Tissue and Organs for Research Resource (HTORR) Grant Number: U420DO1158. To address the high priority areas of research for AD/ADRD that require both post mortem and living patient biospecimen collection that are beyond the scope of HTORR, NDRI is expanding their capabilities to create a new resource, the AD/ADRD Human Biospecimen Resource (ADBR), funded by the active award 3U42OD011158-28S3. In Program Year 2 of the ADBR, NDRI continued to lead the development of the ADBR Advisory Council to obtain ongoing recommendations regarding biospecimen collection and distribution for the ADBR that align with an unmet or under represented need in the field. For the current proposal to continue the progression of the ADBR, NDRI will: 1) identify and authorize/consent distinct cohorts of non-diseased and AD/ADRD post mortem donors 2) coordinate the recovery of AD/ADRD biospecimens, 3) distribute biospecimens and donor data to investigators or store biospecimens to support future high priority area studies, and 4) monitor the performance of the ADBR and maintain guidance for the resource from an ADBR Advisory Council. In doing so, the biospecimen collection and preservation methods will be optimized to the experimental hypotheses and procedures for each ADBR study using NDRI's experience in coordinating standardized procurement, processing, preservation and shipping methods and maintaining industry best practices and standards regarding the donation of human tissue for research. The overall objective of the ADBR is to provide approved investigators with biospecimens from defined cohorts of AD/ADRD and non-diseased control post mortem donors, to support the generation of high-quality, reproducible data for the advancement of AD/ADR research. Relevance: As the most common cause of dementia, AD is a devastating, progressive neurodegenerative disease that affects over 5.7 million Americans (Alzheimer's Association et al, 2018) and has a significant burden on the US healthcare system as well as caregivers. As of yet, there are no disease-modifying treatment options available for AD/ADRD patients, making this a high priority for the research community. The objective of this proposal is to provide biospecimens from post mortem AD/ADRD donors, as well as non- diseased control donors for the AD/ADRD Human Biospecimen Resource (ADBR) that are suitable to support critical lines of investigation that address high priority needs and key issues in the field. OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page